Abstract 102P
Background
KRAS mutation is the most common molecular alteration in non-small cell lung cancer (NSCLC), it can be found in up to 25% of patients with adenocarcinoma. However, KRAS mutations represent a heterogeneous group of diseases not well characterized. This could be explained by the genomic commutations or by the type of point mutation that may affect downstream signaling differently. Given the recent discovery of several effective KRAS G12C inhibitors, interest in this type of mutation is on the rise. According to the literature, KRAS G12C is the predominant mutation (35%) in patients with KRAS-mutant tumors, nevertheless, there is little specific data in our population.
Methods
We selected patients diagnosed with KRAS mutant NSCLC from February 2021 to March 2022 from 4 hospitals in Madrid. KRAS status was determined by using the AVENIO Tumor Tissue Targeted Kit® (a Next Generation Sequencing test). PD-L1 status was determined by immunohistochemistry assay (22C3 pharmDx). Molecular and clinicopathological characteristics were collected and a descriptive analysis was performed.
Results
78 patients were found to have a KRAS mutation and were included in our study. Almost 45% had stage IV disease, 20% stage III and 35% stage I and II. Most tumors were adenocarcinomas (88%) followed by squamous carcinomas (8%). The rest were other histologies and mixed tumors. 30.8% of the patients were KRAS G12C, 29.5% G12D and 24.4% G12V. Paradoxically, in our population, KRAS G12D was more common in the metastatic patient, representing the most frequent mutation (40%), followed by G12C (25%) and G12V (22.8%). PD-L1 status was very similar independent of mutation subtype, being ≥ 50% in 45.8% of KRAS G12C and 42.6% in KRAS non-G12C and <1% in 29.2% of KRAS G12C and 31.5% in KRAS G12C. 34.6% of the patients had one or more commutations. TP53 was the most frequent (37%), followed by others such as MET, STK11, DPYD, PI3K or BRAF mutations, present in around 10% of patients.
Conclusions
As described in our population, KRAS G12C accounts for one third of the KRAS mutations, being susceptible to new treatments. This mutation is more frequent in early stages, being the most frequent KRAS G12D in metastatic patients. PD-L1 status is similar in all high prevalence mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.